Results from London Regional Clinical Genetics services over a 5-year period on germline TP53 testing in women diagnosed with breast cancer at <30 years

BackgroundThe most common cancer diagnosed in germline TP53 pathogenic variant (PV) carriers is premenopausal breast cancer. An increased rate of breast tumour HER2 positivity has been reported in this group. Screening for breast/other cancers is recommended in PV carriers.Objectives1. To assess the frequency of germline TP53 PVs reported diagnostically in women with breast cancer at <30 years of age.2. To evaluate the impact of personal/family history and HER2 status on the likelihood of germline TP53 pathogenic/likely pathogenic variant (PV/LPV) identification.MethodsGenetic test results from patients undergoing diagnostic germline TP53 tests between 2012 and 2017 in the four London Regional Clinical Genetics Services were reviewed. Clinical/pathology data and family history were extracted from genetics files for women diagnosed with breast cancer at <30 years.ResultsThe overall germline TP53 PV/LPV variant detection rate was 9/270=3.3% in all women diagnosed with breast cancer at <30 years and 2/171=1.2% in those with no second/subsequent cancer diagnosis or family history of TP53-spectrum cancers. Breast cancers were significantly more likely to be HER2-positive in TP53 PV/LPV carriers than in non-carriers (p=0.00006).ConclusionsGermline TP53 PVs/LPVs are uncommon among women diagnosed with breast cancer aged <30 years without other relevant personal or family cancer history but have an important clinical impact when identified.

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Impact of direct-to-consumer genetic testing on Australian clinical genetics services

10.1101/2020.03.05.20031963 ◽

2020 ◽

Author(s):

Michael Millward ◽

Jane Tiller ◽

Michael Bogwitz ◽

Helen Kincaid ◽

Shelby Taylor ◽

...

Keyword(s):

Genetic Testing ◽

Genetic Risk ◽

Online Survey ◽

Third Party ◽

Clinical Genetics ◽

Direct To Consumer ◽

Risk Estimates ◽

Genetics Services ◽

Clinical Genetics Services ◽

The Impact

AbstractPurposeThe increasing popularity of direct-to-consumer genetic testing (DTCGT) is thought to be creating a burden on clinical genetic health services worldwide. However, no studies have collected recent evidence regarding the extent of this impact in Australia.MethodsWe administered an online survey to Australian clinical genetics services, asking questions related to DTCGT-related referrals received and outcomes over the past 10 years.ResultsEleven publicly-funded clinical genetics services completed the survey, reporting over 100 DTCGT-related referrals. Most referrals (83%) were made by general practitioners seeking interpretation of DTCGT results. More than 30% of referrals related to imputed genetic risk estimates generated from third-party web-based software tools. Services reported low validation rates for DTCGT results (<10%). Procedures for managing DTCGT referrals and granting appointments were variable between services, with most services (8/11) lacking specific procedures.ConclusionOur study helps quantify the impact of DTCGT on clinical genetics services, and highlights the impact of imputed genetic risk estimates generated from third-party software.

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The impact of ‘uninformative’ BRCA1/2 genetic test results on health professionals, caring for affected and unaffected women with a significant breast cancer family history

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2009.07.017 ◽

2009 ◽

Vol 35 (11) ◽

pp. 1207

Author(s):

Audrey Ardern-Jones ◽

R. Kenen ◽

E. Lynch ◽

R. Doherty ◽

R. Eeles

Keyword(s):

Breast Cancer ◽

Family History ◽

Health Professionals ◽

Genetic Test ◽

Test Results ◽

Breast Cancer Family ◽

Cancer Family ◽

Genetic Test Results ◽

The Impact ◽

Breast Cancer Family History

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BRCA testing concordance with national guidelines for patients with breast cancer in community cancer programs.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1526-1526

Author(s):

Leigh Boehmer ◽

Latha Shivakumar ◽

Christine B. Weldon ◽

Julia Rachel Trosman ◽

Stephanie A. Cohen ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

High Risk ◽

Genetic Test ◽

Breast Conserving Surgery ◽

Test Results ◽

Cancer Genes ◽

National Guidelines ◽

Genetic Test Results ◽

The Impact

1526 Background: Current National Comprehensive Cancer Network guidelines for genetic/familial high-risk assessment state that testing for highly penetrant breast/ovarian cancer genes is clinically indicated for women with early onset (≤ 45 years) or metastatic HER-2 negative breast cancer. A recent Association of Community Cancer Centers (ACCC) survey (N = 95) showed that > 80% of respondents reported ≤ 50% testing rate of patients with breast cancer who met guidelines. Given this disconnect, ACCC partnered with 15 community cancer programs to assess practice gaps and support interventions to improve access to genetic counseling (GC)/testing. Methods: Pre-intervention data from 9/15 partner programs for women diagnosed with stages 0-III breast cancer between 01/01/2017 and 06/30/2019 was collected. De-identified variables included: family history documentation, GC appointment/test results, and timing of results relative to treatment decisions. Results: There were 2691 women with stages 0-III breast cancer. Forty-eight percent (1284/2691) had a documented high-risk family history, 57% (729/1284) of whom had a GC appointment. This was a significantly higher rate of GC compared to the 23% (181/778) of women with no family history and 6% (35/629) of women with no documentation of family history (p < 0.0001). Patients ≤ 45 years old attended a GC appointment 72% (199/278) of the time and 49% (135/278) had genetic test results, with 84% (113/135) receiving results before surgery. For women with test results available before surgery, 37% (119/322) had breast conserving surgery, compared to 60% (144/240) with test results disclosed post-operatively (p < 0.0001). Conclusions: Genetic testing is underutilized in a community cohort of women with breast cancer. Further analysis is needed to understand the impact genetic test results have on surgical decisions. Opportunities exist to improve current rates of appropriate GC/testing. ACCC will share results of quality improvement projects to illuminate which strategies hold promise in reducing the hereditary breast cancer GC/testing practice gap.

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Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2010.33.5232 ◽

2012 ◽

Vol 30 (6) ◽

pp. 587-592 ◽

Cited By ~ 256

Author(s):

Eitan Amir ◽

Naomi Miller ◽

William Geddie ◽

Orit Freedman ◽

Farrah Kassam ◽

...

Keyword(s):

Breast Cancer ◽

Prospective Study ◽

Treatment Plan ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Her2 Status ◽

Primary Tumors ◽

Receptor Status ◽

Metastatic Recurrence ◽

The Impact

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

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Impact of direct-to-consumer genetic testing on Australian clinical genetics services

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2020.103968 ◽

2020 ◽

Vol 63 (9) ◽

pp. 103968

Author(s):

Michael Millward ◽

Jane Tiller ◽

Michael Bogwitz ◽

Helen Kincaid ◽

Shelby Taylor ◽

...

Keyword(s):

Genetic Testing ◽

Clinical Genetics ◽

Direct To Consumer ◽

Genetics Services ◽

Clinical Genetics Services

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Clinicopathological and Prognostic Value of CD24 Expression in Breast Cancer: A Meta-Analysis

The International Journal of Biological Markers ◽

10.5301/jbm.5000254 ◽

2017 ◽

Vol 32 (2) ◽

pp. 182-189

Author(s):

Gao Liu ◽

Guo-Xing Liu ◽

Yu Fang ◽

Zhen-Yu Cao ◽

Hui-Hui Du ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Pooled Analysis ◽

Tnm Stage ◽

Her2 Status ◽

Relative Risk Ratio ◽

The Impact

Background A number of studies have been conducted to explore the relationship between CD24 expression and the prognosis of breast cancer; however, the results remain inconsistent. Therefore, we performed this meta-analysis to clarify the impact of CD24 expression on clinicopathological features and prognosis of breast cancer. Methods A comprehensive literature search for relevant studies was performed, and statistical analysis was conducted using Stata software. Results Twenty studies, including 5,179 cases, were included in this meta-analysis. The pooled analysis indicated that CD24 expression was associated with lymph node invasion (odds ratio [OR] = 0.68, for negative vs. positive, 95% confidence interval [95% CI], 0.53-0.87, p = 0.002) and TNM stage (OR = 0.63, for I + II vs. III + IV, 95% CI, 0.49-0.81, p<0.001). The prognosis analysis also suggested CD24 overexpression indicated a poorer 5-year overall survival (OS) rate (relative risk ratio [RR] = 0.93, 95% CI, 0.86-0.99, p = 0.03) and 5-year disease-free survival (DFS) rate (RR = 0.90, 95% CI, 0.83-0.98, p = 0.02). However, CD24 expression had no correlation with tumor size, tumor grade, distance metastasis, estrogen receptor (ER) status, progesterone receptor (PR) status, or HER2 status. Conclusions Our results suggest that higher CD24 expression is significantly associated with lower OS rate, lower DFS rate and some clinicopathological factors such as lymph node invasion and TNM stage. This meta-analysis suggested that CD24 is an efficient prognostic factor in breast cancer.

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Mortality and Risk of Cancer After Prophylactic Bilateral Oophorectomy in Women With a Family History of Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pky034 ◽

2018 ◽

Vol 2 (3) ◽

Cited By ~ 1

Author(s):

Julie Abildgaard ◽

Magnus Glindvad Ahlström ◽

Gedske Daugaard ◽

Dorte Lisbet Nielsen ◽

Anette Tønnes Pedersen ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Rate Ratio ◽

Bilateral Oophorectomy ◽

Family History Of Cancer ◽

Increased Risk ◽

History Of ◽

Risk Of Cancer ◽

The Impact ◽

History Of Cancer

Abstract Background Current international guidelines recommend systemic hormone therapy (HT) to oophorectomized women until the age of natural menopause. Despite an inherited predisposition to estrogen-dependent malignancies, the guidelines also apply to women oophorectomized because of a family history of cancer. The objective of this study was to investigate the impact of HT on mortality and risk of cancer in women oophorectomized because of a family history of cancer. Methods A nationwide, population-based cohort was used to study women oophorectomized because of a family history of cancer (n = 2002). Comparison cohorts included women from the background population individually matched on age (n = 18 018). Oophorectomized women were subdivided into three groups: oophorectomized at 1) age 45 years or younger not using HT, 2) age 45 years or younger using HT, 3) older than age 45 years, and their respective population comparison cohorts. Results Women oophorectomized at age 45 years or younger using HT had increased overall mortality (mortality rate ratio [MRR] = 3.45, 95% confidence interval [CI] = 1.53 to 7.79), mortality because of cancer (MRR = 5.67, 95% CI = 1.86 to 17.34), and risk of overall cancer (incidence rate ratio [IRR] = 3.68, 95% CI = 1.93 − 6.98), primarily reflected in an increased risk of breast cancer (IRR = 4.88, 95% CI = 2.19 − 10.68). Women oophorectomized at age 45 years or younger not using HT and women oophorectomized at older than age 45 years did not have increased mortality, mortality because of cancer, or risk of overall cancer, but they had increased risk of breast cancer (IRR = 2.64, 95% CI = 1.14 to 6.13, and IRR = 1.72, 95% CI = 1.14 to 2.59, respectively). Conclusions Use of HT in women oophorectomized at age 45 years or younger with a family history of cancer is associated with increased mortality and risk of overall cancer and breast cancer. Our study warrants further investigation to establish the impact of HT on mortality and cancer risk in oophorectomized women with a family history of cancer.

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